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Cited by 288

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An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals

Open access
Carbonell, Pablo, Jervis, Adrian J., Robinson, Christopher J., Yan, Cunyu, Dunstan, Mark, Swainston, Neil, Vinaixa, Maria, Hollywood, Katherine A., Currin, Andrew, Rattray, Nicholas J. W., Taylor, Sandra, Spiess, Reynard, Sung, Rehana, Williams, Alan R., Fellows, Donal, Stanford, Natalie J., Mulherin, Paul, Le Feuvre, Rosalind, Barran, Perdita, Goodacre, Royston, Turner, Nicholas J., Goble, Carole, Chen, George Guoqiang, Kell, Douglas B., Micklefield, Jason, Breitling, Rainer, Takano, Eriko, Faulon, Jean-Loup, Scrutton, Nigel S.·2018·Communications Biology

Abstract

The microbial production of fine chemicals provides a promising biosustainable manufacturing solution that has led to the successful production of a growing catalog of natural products and high-value chemicals. However, development at industrial levels has been hindered by the large resource investments required. Here we present an integrated Design–Build-Test–Learn (DBTL) pipeline for the discovery and optimization of biosynthetic pathways, which is designed to be compound agnostic and automated throughout. We initially applied the pipeline for the production of the flavonoid (2 S)-pinocembrin in Escherichia coli, to demonstrate rapid iterative DBTL cycling with automation at every stage. In this case, application of two DBTL cycles successfully established a production pathway improved by 500-fold, with competitive titers up to 88 mg L−1. The further application of the pipeline to optimize an alkaloids pathway demonstrates how it could facilitate the rapid optimization of microbial strains for production of any chemical compound of interest.

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Metadata

Authors
Carbonell, P., Jervis, A. J., Robinson, C. J., Yan, C., Dunstan, M., Swainston, N., Vinaixa, M., Hollywood, K. A., Currin, A., Rattray, N. J. W., Taylor, S., Spiess, R., Sung, R., Williams, A. R., Fellows, D., Stanford, N. J., Mulherin, P., Le Feuvre, R., Barran, P., Goodacre, R., Turner, N. J., Goble, C., Chen, G. G., Kell, D. B., Micklefield, J., Breitling, R., Takano, E., Faulon, J.-L., & Scrutton, N. S.
Venue
Communications Biology
Published
2018-06-08
Volume
1
Issue
1
Pages
66-66
ISSN
2399-3642 (ISSN-L)
OpenAlex
W2806394571
Cited by
288
References
1
FWCI
7.61
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals. https://app.cochat.ai/papers/10.1038/s42003-018-0076-9
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Carbonell, P., Jervis, A. J., Robinson, C. J., Yan, C., Dunstan, M., Swainston, N., Vinaixa, M., Hollywood, K. A., Currin, A., Rattray, N. J. W., Taylor, S., Spiess, R., Sung, R., Williams, A. R., Fellows, D., Stanford, N. J., Mulherin, P., Le Feuvre, R., Barran, P., . . . Scrutton, N. S. (2018). An automated Design-Build-Test-Learn pipeline for enhanced microbial production of fine chemicals. Communications Biology. https://doi.org/10.1038/s42003-018-0076-9

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.